Acute cerebral infarction: pathophysiology and modern treatment concepts

Summary This review focuses on the pathophysiological changes in acute cerebral ischemia, with special emphasis on disturbances of the cerebral blood flow (CBF) and the associated penumbra concept. Alternatively, the model of peri-infarct depolarization is demonstrated. Metabolic and molecular changes caused by cerebral ischemia and reperfusion are discussed, namely energy failure, release of glutamate with an excitatoric burst, calcium influx in neurons, generation of free radicals, activation of different proteases, disturbances of protein synthesis, induction of gene expression and apoptosis, loss of membrane integrity, edema formation and microvascular disturbances. In summary, the pathophysiological changes after focal cerebral ischemia and reperfusion are most adequately described by a network of interacting different mechanisms of tissue alterations. The simple concept of a cascade of ischemic effects which would be easy to block seems to be less applicable. A time window of approximately 6 h for the acute stroke therapy is postulated on the base of the above mentioned pathophysiological changes. The recently introduced treatment regimen with optimized basic treatment, recanalization using thrombolysis and neuroprotection by different agents is presented. Different modes of a possible intervention are discussed. Modern concepts of stroke therapy including stroke-unit care and thrombolysis with add-on neuroprotection seem to have potential for improving the outcome of acute stroke patients.      

Lindane inhibition of [35S]TBPS binding to the GABAA receptor in rat brain.

The inhibition of [³⁵S]t-butylbicyclophosphorothionate ([³⁵S]TBPS) binding to the GABA_A receptor by the insecticide γ-hexachlorocyclohexane, lindane, was studied in several brain regions and using different membrane preparation methods, both in vitro and after dosing the animals with the chemical. In the latter studies, the amount of lindane remaining in the membrane suspensions used for binding assays was determined. In vitro data showed values of IC₅₀ from 150 to 1675 nM, varying in function of the membrane preparation method used. This may account for the discrepancies in IC₅₀ values found in the literature. IC₅₀ values within the range of 150–250 nM were determined using extensively washed membranes from several brain regions, so no evidence arose for brain regional differences in the affinity of lindane for the TBPS binding site. After different schedules of acute treatment with lindane, we found a manifest relationship between the extent of the observable inhibition of [³⁵S]TBPS binding and the lindane amount remaining in the membrane suspensions used for binding assays. This relationship was in good agreement with the in vitro data, so no support for an in vivo acute regulation of the binding site was obtained.     

Impaired water metabolism and cerebral oedema following experimental subarachnoid haemorrhage in rats1

The acute phase of subarachnoid haemorrhage (SAH) is frequently associated with an impaired water metabolism and a disposition to cerebral oedema. For study of the pathogenesis of brain oedema following SAH, an experimental model of SAH was created in the rat The diuretic curves after water loading, the brain water and electrolyte contents and the plasma and cerebrospinal fluid arginine vasopressin (AVP) levels were examined in rats with SAH. Following a water load, a significant water retention and increases in brain water and sodium contents were observed after subarachnoid bleeding. Plasma and cerebrospinal fluid AVP levels were also elevated following SAH. It can be concluded that AVP plays important roles in the development of antidiuresis after water loading and in the disturbance of the brain water and electrolyte balance following experimental SAH.     

Phaeohyphomycosis caused by Bipolaris spicifera: An informative case

A case of phaeohyphomycosis caused by Bipolaris spicifera involving the brain and sinuses is presented. The patient survived following surgery and ketoconazole therapy, which successfully treated both the sinus and the brain infections.     

川芎嗪对脑外伤患者血栓素、前列腺环素及颅内压的影响

28例重度脑外伤患者分为川药嗪治疗组和一般治疗对照组,两组病人均于用药前和用药后3小时测定血浆和脑室内脑脊液(VCSF)中血栓素代谢产物(TXB_2)前列腺环素代谢产物6—酮—PGF_(la)(6KP)和颅内压。结果表明:两组治疗前血浆、VCSF中TXB_2及T/K均明显高于正常献血员对照组,川芎嗪能降低脑外伤患者血浆、VCSF中TXB_2及T/K值,对颅内压则无明显影响。提示川芎嗪能抑制脑外伤对血小板的激活、纠正循环血中TXA_2—PGI_2平衡失调,从而改善脑微循环。     

Development of cranial flexure and Rathke's pouch in the chick embryo

Experiments were done to investigate the cause of the cranial (mesencephalic) flexure of the chick brain during stages 10 to 14. Measurements of the length and thickness of the roof and floor of the mesencephalon gave values similar to the values obtained previously by others. The labeling index was determined in the roof and floor of the prosencephalon, mesencephalon, and rhombencephalon as a preliminary measure of cell division. The labeling index was about the same in all regions, and was high enough to suggest that most of the cells were dividing. The labeling indices did not suggest that differential growth was caused by differential rates of cell division in the roof and floor of the mesencephalon. It was found through time lapse photography that the foregut and heart remained stationary along the rostrocaudal axis, whereas the prosencephalon moved rostrally and the mesencephalon underwent flexure. Measurements suggested that the neural tube cranial to the otic primordium grew in volume exponentially at a rate consistent with the labeling index. The rostral tip of the neural tube was observed to be linked to the rostral tip of the foregut by the ectoderm that formed Rathke's pouch at the neural tube and the pharyngeal membrane (prospective stomodeum) at the foregut. As the neural tube grew in length, the link between the neural tube and the foregut did not. We suggest that because of this link, the growing neural tube had to bend around the foregut, forming the cranial flexure, and the ectoderm folded where it attached to the prosencephalon, forming Rathke's pouch. © 1994 Wiley-Liss, Inc.     

A prospective radiologic and neurologic follow-up study of 61 HIV-1 -infected subjects: early beginning and slow progression of brain atrophy

The course of the organic brain disease caused by human immunodeficency virus (HIV-1) was evaluated in a follow-up study. The primary material included 200 consecutive HIV-1 infected persons. Sixty-one subjects, in whom other brain-affecting factors were excluded, consented to the follow-up. They underwent 278 radiologic examinations: computed tomography, magnetic resonance imaging, or a combination of both (mean 4.6 examinations/subject). Clinical neurologic status and, in 40 subjects, cognitive performance were repeatedly evaluated. Sixteen subjects were followed up until death and 11 of them were autopsied. Median follow-up time was 27 mo (range 2.5–66 mo). The most common radiologic finding was atrophy, found in 19 subjects at study entry and developing in 10 subjects during the study. Twenty-four subjects (39%) showed the development and/or progression of atrophy. Atrophic changes progressed most rapidly in acquired immunodeficiency syndrome (AIDS), but mild developing/progressive atrophy was found even in 33% of asymptomatic or neurologically intact subjects. Cognitive and radiologic worsening were simultaneous in 6/7 subjects with declining neuropsychologic test performance. Signal intensity changes including HIV-1 leukoencephalopathy appeared in AIDS patients with clear cognitive decline.     

Intracranial alveolar echinococcosis: CT and MRI

Intracranial alveolar echinococcosis is uncommon. We report a patient with right frontal lobe and palpebral lesions secondary to a primary hepatic focus with secondary lesion in the lung. The intracranial and palpebral cystic masses were totally removed and both proved to be alveolar hydatid cysts. An unusual feature in this case is CT and MRI demonstration of dural and bony extension.     

Intracerebral penetration of carteolol hydrochloride in rats

To elucidate the penetrability of carteolol, a β-adrenoceptor antagonist (β-blocker) into the brain of rats, intracerebral and serum concentrations of the compound were determined in male rats receiving single or repetitive oral administration of carteolol hydrochloride at 30 mg/kg. The time-course of the intracerebral concentration of carteolol following single IV administration of the compound at 10 and 30 mg/kg was also studied in male rats. A high-performance liquid chromatography method was used to determine the intracerebral and serum concentrations. Following single oral dosing, the intracerebral concentration of carteolol reached a maximum of 0.074 μg/g at 2 h postdosing and declined with a half-life of 3.7 h, and the C_max and AUC of carteolol in the brain were 12.5% and 19.8% of those in serum. The intracerebral and serum concentrations of carteolol were determined in male rats receiving repetitive oral dosing of the compound once daily for 7 days. The concentration of carteolol in the brain and serum at 1 h postdosing varied within a range of 0.059–0.091 μg/g and 0.321–0.443 μg/ml, respectively, throughout the dosing period, showing no changes in the penetrability of the compound into the brain due to repeated dosing. The concentration of carteolol in the brain and serum increased in a dose-dependent manner in rats receiving a single IV administration of the compound. The elimination half-life of carteolol in the serum and brain was 0.6–0.8 h and 1.3–1.7 h, respectively, in rats following single IV dosing of the compound. The half-life in the brain was about twice as long as that in the serum. The brain to serum concentration ratio was 0.306:0.499. From the above results, it was concluded that carteolol is distributed from the circulation to the brain with low penetrability. Received: 30 October 1996/Final version: 16 December 1996